The nanoemulsions are heterogeneous polyphasic systems wherein at least one phase is dispersed in the form of nano-particles (nanodroplets) in the outer continuous aqueous phase. As for the classical emulsions, the presence of a surface-active system, which is capable of decreasing the interface tension that is very high in these systems, is essential due to the high number of dispersed-phase particles. The surfactant creates an amphiphilic crown on the surface of the dispersed-phase droplets, thereby reducing the interface tension.
Due to the reduced micelle diameter that minimises the possibility of interaction with light and ultraviolet quanta (hv), the nanoemulsions appear transparent and translucent and take on a characteristic “bluish Tyndall” colouring, characterised by a tendency to opalescent blue. The Tyndall effect is a light dispersion phenomenon due to the presence of dispersed particles with a size comparable to that of the incident light wavelength. Thus, in such dispersions, the incident light is reflected in every direction.
In order to be able to obtain nanoemulsions, it is necessary to exert strong stresses in terms of kinetic and thermal energy during emulsification, as well as the use of emulsifiers designed to decrease in a very effective way the micelle interface tension that opposes the diameter reduction thereof, according to LaPlace and Stokes-Einstein rules.
According to LaPlace rule, the pressure gradient between the outer and inner phases (ΔP) corresponds to twice the ratio of the liquid/liquid interface tension between the inner phase micelle (T) and the micelle radius (r), that is: ΔP=2T/r. From this equation, the tight connection between the inner phase micelle radius and the inner and outer differential pressure is inferred, which is expressed as the required force to be applied to the biphasic system in order to minimise the radius and interface tension of the micelle itself. In fact, the pressure, being inversely proportional to the radius, increases with the decrease of the latter and thus the ΔP value corresponds to the pressure to be overcome in order to decrease the particle size. For this reason, not only high concentrations of surfactants that decrease the interface tension must be used, but also considerable kinetic and thermal forces must by applied in order to reach a stability.
The nanoemulsion stability also depends on Stokes-Einstein rule, according to which v=2r2 (d1−d2) g/9η, wherein v represents the sedimentation rate, r the radius of the dispersed particles, d1 the density of the dispersed particles, d2 the density of the continuous phase, g the gravitational constant and η corresponds to the viscosity of the continuous phase. This rule regulates the sedimentation rate for a supposedly spherical particle, pointing out that the sedimentation rate is proportional to the size of the dispersed particle and thus confirming the importance of the surface-active system. In the case of nanoemulsions, wherein the inner particles exhibit a diameter smaller than 0.5 μm, such a rule becomes less important, in that the particles are not subjected to the acceleration of gravity, but are subjected to Brownian motions. Therefore, in order for the particles to sediment, a force higher than the gravitational one is necessary.
The nanoemulsions, as they are not equilibrium systems, can not form spontaneously because the system attains a thermodynamic stability only if the interface tension reaches values that are sufficiently low such that the positive interface energy can be compensated for. The known methods for the formation of nanoemulsions are of a mechanical type and comprise the use of high-energy instruments such as, for example, high-energy mixers, high-pressure homogenizers, or ultrasounds. Using such instruments allows to deform the forces that keep the particles joined, such that they can break into smaller units. However, in order to obtain such a result, it is necessary to overcome the pressure gradient described by LaPlace rule, for instance by adding surfactants. Nevertheless, these preparation methods are complex and costly, therefore simpler solutions based on exploitation of the chemo-physical properties of the system have been sought.
One first method of this kind is based on the so-called “Taylor instability” and consists in modifying the formulation such that the micro-emulsion particles merge and break into smaller particles at the time when the interface tension is increased. However, due to the high degree of coalescence that develops during the processing, the method turns out to be rather complex. In fact, the droplets tend to combine rapidly, thereby forming bigger drops. It is however possible to obviate this phenomenon by exploiting the Phase Inversion Temperature (PIT), thanks to which a liquid crystal layer can form, which is able to encapsulate the droplets.
A second type of method exploits phase inversion. One first possibility is based on the so-called “catastrophic phase inversion”, wherein an emulsion containing water-in-oil drops suddenly turns into an oil-in-water dispersion or vice versa. Recent researches have shown that in some cases such an inversion can occur by passing through an intermediate structure designated as “multiple emulsion”, wherein the continuous phase is able to deform and create smaller drops embedded in the bigger ones. When this multiple emulsion finally breaks it can release small droplets. The second possibility is instead based on the traditional phase inversion, wherein the spontaneous reorganisation of the surfactant micelles is exploited.
The size of the droplets within the nanoemulsions is so small that gravity has no effect on them: they will not sediment until the drop size increases by coalescence through Brownian motions or other processes called “Ostwald ripening”, which are controlled by the pressure gradient of Laplace rule existing among droplets of different sizes. Such sedimentation mechanisms can be, as previously already stated, inhibited by using a set of appropriate solvents and preparing an emulsion the most monodisperse as possible.
Therefore, there exists a need for a stable nanoemulsion having a reduced micelle size, which is able to carry a wide range of pharmaceutical, cosmetic or foodstuff active principles, and the making of which does not require the use of complex or costly methods or devices.